Method for preparing substituted 4-aminoindane derivatives

Abstract

The present invention relates to a method for preparing substituted 4-aminoindane derivatives of the general formula (I) by rearrangement of compounds of the formula (II) in HF, wherein R 1 , R 2 , R 3 , R 4 , and R 5 have the definitions as specified in the description.

The invention claimed is: 
     
       1. A process for preparing substituted 4-aminoindane derivative of general formula (I) 
       
         
           
           
               
               
           
         
         in which 
         R 1  is hydrogen, (C 1 -C 8 )-alkyl or (C 3 -C 8 )-cycloalkyl, 
         R 2 , R 3  each are mutually independently hydrogen, (C 1 -C 8 )-alkyl or (C 3 -C 8 )-cycloalkyl, 
         R 4  is CO—(C 1 -C 4 )-alkyl, 
         R 5  is hydrogen, halogen or (C 1 -C 4 )-alkyl, 
         comprising reacting a compound of Formula (II) 
       
       
         
           
           
               
               
           
         
         with anhydrous hydrogen fluoride. 
       
     
     
       2. The process according to  claim 1 , wherein
 R 1  is hydrogen or (C 1 -C 4 )-alkyl 
 R 2  and R 3  each are mutually independently hydrogen or (C 1 -C 4 )-alkyl, 
 R 4  is CO—(C 1 -C 4 -alkyl), 
 R 5  is hydrogen or (C 1 -C 4 )-alkyl. 
 
     
     
       3. The process according to  claim 1 , wherein
 R 1  is hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl, 
 R 2  and R 3  each are mutually independently methyl, ethyl, n-propyl, isopropyl or n-butyl, 
 R 4  is CO—CH 3 , 
 R 5  is hydrogen or methyl. 
 
     
     
       4. The process according to  claim 1 , wherein
 R 1 , R 2  and R 3  each are methyl, 
 R 4  is CO—CH 3 , 
 R 5  is hydrogen. 
 
     
     
       5. The process according to  claim 1 , wherein the process is carried out at a temperature in a range of from 0° C. and 50° C. 
     
     
       6. The process according to  claim 1 , wherein the process is carried out at a temperature in a range of from 0° C. and 40° C. 
     
     
       7. The process according to  claim 1 , wherein the process is carried out at a temperature in a range of from 0° C. and 30° C. 
     
     
       8. The process according to  claim 1 , wherein the process is carried out at a temperature in a range of from 10° C. and 20° C. 
     
     
       9. The process according to  claim 1 , wherein an amount of used hydrogen fluoride is in the range of 1 to 100 molar equivalents based on the total amount of compound of formula (II). 
     
     
       10. The process according to  claim 1 , wherein reaction time of hydrogen fluoride with compounds of formula (II) is between 1 and 24 hours. 
     
     
       11. A process for preparation of a compound of formula (III) 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is hydrogen, (C 1 -C 8 )-alkyl or (C 3 -C 8 )-cycloalkyl, 
 R 2 , R 3  each are mutually independently hydrogen, (C 1 -C 8 )-alkyl or (C 3 -C 8 )-cycloalkyl, 
 R 4  is CO—(C 1 -C 4 )-alkyl, 
 R 5  is hydrogen, halogen or (C 1 -C 4 )-alkyl, 
 
       comprising the process according to  claim 1  and further comprising hydrolyzing the compound of formula (I) in water to obtain the compound of formula (III). 
     
     
       12. The process according to  claim 11 , wherein the process is carried out at a temperature in a range of from 50° C. to 100° C. 
     
     
       13. The process according to  claim 1 , wherein an amount of used hydrogen fluoride is in a range of 5 to 30 molar equivalents based on the total amount of compound of formula (II). 
     
     
       14. The process according to  claim 1 , wherein an amount of used hydrogen fluoride is in a range of 5 to 20 molar equivalents based on the total amount of compound of formula (II). 
     
     
       15. The process according to  claim 1 , wherein a reaction time of hydrogen fluoride with compounds of formula (II) is between 10 and 22 hours.